A5082679623- Genetic and Kidney Cyst Diseases
- Hedgehog Signaling Pathway Studies
- Renal and related cancers
- Epigenetics and DNA Methylation
- Sexual Differentiation and Disorders
- Urological Disorders and Treatments
- Genetic Syndromes and Imprinting
- Drug Transport and Resistance Mechanisms
- Protist diversity and phylogeny
- Metabolism and Genetic Disorders
- Hormonal and reproductive studies
- Cystic Fibrosis Research Advances
- Fetal and Pediatric Neurological Disorders
- Clinical Nutrition and Gastroenterology
- Silk-based biomaterials and applications
- Porphyrin Metabolism and Disorders
- Clostridium difficile and Clostridium perfringens research
- Urologic and reproductive health conditions
- Gut microbiota and health
- Pediatric Hepatobiliary Diseases and Treatments
- Tryptophan and brain disorders
- Congenital Anomalies and Fetal Surgery
- Cancer-related Molecular Pathways
- Cellular transport and secretion
- Long-Term Effects of COVID-19
Inserm
2012-2024
Sorbonne Université
2015-2024
Centre de Recherche Saint-Antoine
2018-2024
Assistance Publique – Hôpitaux de Paris
2018-2024
Hôpital Saint-Antoine
2022-2024
Fédération Hospitalo-Universitaire, Paris Center for Microbiome Medicine
2024
University of Massachusetts Chan Medical School
2014-2023
Sorbonne Paris Cité
2022
École Normale Supérieure - PSL
2018
Laboratoire des Biomolécules
2018
The vertebrate hedgehog pathway is organized in primary cilia, and components relocate into or out of cilia during signaling. Defects intraflagellar transport (IFT) typically disrupt ciliary assembly attenuate Determining whether IFT drives the movement difficult due to requirement for building cilia. Unlike most proteins, IFT27 dispensable formation but affects signaling similarly other IFTs, allowing us examine its role dynamics Activating at points along Ift27 mutant cells showed that...
Motile and non-motile cilia play critical roles in mammalian development health. These organelles are composed of a 1000 or more unique proteins, but their assembly depends entirely on proteins synthesized the cell body transported into cilium by intraflagellar transport (IFT). In mammals, malfunction due to IFT dysfunction results complex developmental phenotypes that affect most organs. contrast, disruption motile function causes subfertility, left-right axis, recurrent airway infections...
Recent studies identified a previously uncharacterized gene C5ORF42 (JBTS17) as major cause of Joubert syndrome (JBTS), ciliopathy associated with cerebellar abnormalities and other birth defects. Here we report the first Jbts17 mutant mouse model, Heart Under Glass (Hug), recovered from forward genetic screen. Exome sequencing Hug S235P missense mutation in homolog JBTS17 (2410089e03rik). mutants exhibit multiple defects typical ciliopathies, including skeletal dysplasia, polydactyly,...
Abstract The local immune-inflammatory response elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still poorly described, as well the extent to which its characteristics may be associated with outcome of critical Coronavirus disease 2019 (COVID-19). In this prospective monocenter study, all consecutive COVID-19 critically ill patients admitted from February December 2020 and explored fiberoptic bronchoscopy bronchoalveolar lavage (BAL) were included....
Hair follicle morphogenesis requires precisely controlled reciprocal communications, including hedgehog (Hh) signaling. Activation of the Hh signaling pathway relies on primary cilium. Disrupting ciliogenesis results in hair defects due to attenuated signaling; however, loss cilia makes it impossible determine whether phenotypes these mutants are caused by cilia, disruption signaling, or a combination events. In this study, we characterized function Ift27, which encodes subunit...
Tryptophan, an essential amino acid, and its metabolites are involved in many physiological processes including neuronal functions, immune system, gut homeostasis. Alterations to tryptophan metabolism associated with various pathologies such as neurologic, psychiatric disorders, inflammatory bowel diseases (IBD), metabolic cancer. It is consequently critical develop a reliable, quantitative method for the analysis of downstream from kynurenine, serotonin, indoles pathways. An LC-MS/MS was...
Background: Human-induced pluripotent stem cell-derived hepatocytes (iHeps) have been shown to considerable potential in liver diseases, toxicity, and pharmacological studies. However, there is a growing need obtain iHeps that are truly similar primary adult terms of morphological features functions. We generated such human iHeps, self-assembled as organoids (iHep-Orgs). Methods: iPSC-derived hepatoblasts were into spheroids differentiated mature modulating final step differentiation....
Short chain fatty acids (SCFAs) are primarily produced in the caecum and proximal colon via bacterial fermentation of undigested carbohydrates that have avoided digestion small intestine. Increasing evidence supports critical role SCFAs play health homeostasis. Microbial SCFAs, namely butyric acid, serve as a principal energy source for colonocytes, their production is essential gut integrity. A direct link between some human pathological conditions, such inflammatory bowel disease,...
The 13 subtypes of oral-facial-digital syndrome (OFDS) belong to the heterogeneous group ciliopathies. Disease-causing genes encode for centrosomal proteins, components transition zone or proteins implicated in ciliary signaling. A unique consanguineous family presenting with an unclassified OFDS skeletal dysplasia and brachymesophalangia was explored. Homozygosity mapping exome sequencing led identification a homozygous mutation IFT57, which encodes protein transport. caused splicing...
Article25 October 2022Open Access Transparent process Loss of primary cilia promotes inflammation and carcinogenesis Conception Paul Institut de Génétique Moléculaire Montpellier, Univ CNRS, Label "Equipe FRM", France Contribution: Conceptualization, Formal analysis, Investigation, Methodology Search for more papers by this author Ruizhi Tang orcid.org/0000-0001-6512-845X Ciro Longobardi orcid.org/0000-0003-4965-9976 Center Experimental Molecular Medicine, Cancer Amsterdam, Amsterdam UMC,...
Introduction Bile acids (BA) influence germination and growth of Clostridium difficile. Ursodeoxycholic acid (UDCA), a BA minor in human, used for cholestatic liver diseases, inhibits C.difficile vitro, but was never tested vivo with an infectious challenge versus control. We hypothesized that UDCA could prevent CDI. evaluated the effects on vitro hamsters, pharmacokinetics study challenge. Then, we studied CDI incidence UDCA–treated patients. Methods C.difficile, 0.01%, 0.05% 0.1% UDCA....
In children with premature pubarche (PP), late onset 21-hydroxylase deficiency (21-OHD), also known as non-classical congenital adrenal hyperplasia (NCCAH), can be routinely ruled out by an adrenocorticotropic hormone (ACTH) test. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a quantitative assay of the circulating steroidome obtained from single blood sample. We hypothesized that, applying multivariate machine learning (ML) models to basal steroid profiles and clinical...
The interactions between viruses and actin cytoskeleton have been widely studied. We showed that rotaviruses remodel microfilaments in intestinal cells demonstrated this was due to the VP4 spike protein. Microfilaments mainly occur apical domain of infected polarized enterocytes favor exit viral progeny. present work aims at identification molecular determinants actin-VP4 interactions. used various deletion mutants were transfected into Cos-7 analyzed by immunofluorescence confocal...
Drug-induced cholestasis is mostly intrahepatic and characterized by alterations of bile canaliculi dynamics morphology as well accumulation acids (BAs) in hepatocytes. However, little information exists on first changes BA content profile induced cholestatic drugs human liver. In this study, we aimed to analyze the effects a large set noncholestatic presence physiological serum concentrations 60-fold higher levels 9 main BAs cellular using HepaRG were measured cell layers (cells +...
Although 17-hydroxyprogesterone (17OHP) has historically been the steroid assayed in diagnosis of congenital adrenal 21-hydroxylase deficiency (CAH-21D), its C11-hydroxylated metabolite, 21-deoxycortisol (21DF), which is strictly origin, parallel this pathology. This (21DF) oxidized by 11beta-hydroxysteroid dehydrogenase type 2 into 21-deoxycortisone (21DE). In context CAH-21D confirmation testing, confounding factors (such as intensive care unit admission, stress, prematurity, early...
Motile and non-motile cilia are critical to mammalian development health. Assembly of these organelles depends on proteins synthesized in the cell body transported into cilium by intraflagellar transport (IFT). A series human mouse IFT74 variants were studied understand function this IFT subunit. Humans missing exon 2, which codes for first 40 residues, presented an unusual combination ciliary chondrodysplasia mucociliary clearance disorders while individuals carrying biallelic splice site...
Neonatal screening for congenital adrenal hyperplasia (CAH) faces many specific challenges. It must be done using a performant analytical approach that combines sensitivity and specificity to capture the potential causes of mortality during first week life, such as salt wasting glucocorticoid deficiency. Here, we confirm maternal inhaled corticosteroid intake pregnancy is possible cause missed CAH diagnosis. Thanks liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)...